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STOPP: Serelaxin To Lower Portal Pressure

Sponsor
University of Edinburgh (Other)
Overall Status
Completed
CT.gov ID
NCT02669875
Collaborator
Novartis Pharmaceuticals (Industry), NHS Lothian (Other)
15
Enrollment
1
Location
2
Arms
10.4
Actual Duration (Months)
1.4
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Portal hypertension (an increase in blood pressure in the portal vein that carries the blood from the intestine and spleen to the liver) underlies most of the serious complications of liver cirrhosis. This randomised placebo controlled study in people with liver cirrhosis evaluates the acute effects serelaxin (RLX030) infusion on portal hypertension and liver blood flow.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

This study will investigate the effects of the investigational drug serelaxin (a recombinant form of the peptide human relaxin-2) on portal hypertension in patients with liver cirrhosis. The investigators will measure portal pressure by hepatic venous pressure gradient (HVPG) and hepatic blood flow by indocyanine green (ICG) clearance to evaluate the potential benefits of the drug. In a recently completed small exploratory open-label phase 2 study (EudraCT no. 201200023626, NCT01640964), Part B demonstrated that serelaxin can lower portal pressure.

Study Design

Study Type:
Interventional
Actual Enrollment :
15 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Serelaxin To Lower Portal Pressure in Patients With Cirrhosis and Portal Hypertension
Actual Study Start Date :
Oct 18, 2017
Actual Primary Completion Date :
Aug 31, 2018
Actual Study Completion Date :
Aug 31, 2018

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Serelaxin

IV infusion of serelaxin (RLX030) for 2 hours

Drug: Serelaxin
Serelaxin solution diluted in 5% glucose volume/volume (v/v) solution
Other Names:
  • RLX030
  • Recombinant human relaxin-2

    		•
    Placebo Comparator: Placebo

    IV infusion of placebo (20mM sodium acetate pH5) matched to serelaxin for 2 hours

    Drug: Placebo
    Placebo solution (20mM sodium acetate pH5) diluted in 5% v/v glucose solution

    Outcome Measures

    Primary Outcome Measures

    1. Change from baseline in fasting hepatic venous pressure gradient (HVPG) [Baseline, after 2 hours]

    Secondary Outcome Measures

    1. Change from baseline in fasting hepatic venous pressure gradient (HVPG) [Baseline, after 1 hour]

    2. Change from baseline in fasting hepatic blood flow [Baseline, after 2 hours]

      Measured from the concentration of indocyanine green (ICG) in the hepatic venous blood vs peripheral venous blood using the Fick Principle

    3. Change from baseline in inferior vena cava pressure [Baseline, after 2 hours]

    4. Change from baseline in cardiac index [Baseline, after 2 hours]

    5. Change from baseline in systemic vascular resistance index [Baseline, after 2 hours]

    6. Number of participants with adverse events [4 weeks]

      Adverse events (AE) reporting will be summarized based on number of patients reported with abnormal laboratory values, clinically significant AE, serious adverse events or death

    7. Change from baseline in blood biomarker measurements [Baseline, after 2 hours]

    8. Change from baseline in aortic pulse wave velocity [Baseline, after 2 hours]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. Male or female adult subjects over 18 years of age

    2. Able to provide written informed consent and able to understand and willing to comply with the requirements of the study

    3. Clinical imaging-diagnosed or biopsy-proven liver cirrhosis of any aetiology

    4. Evidence of portal hypertension either on imaging or previous endoscopy

    5. Patients with large/grade 3 varices as identified by endoscopy within 6 months of screening must be in an endoscopic band ligation programme at the time of study entry

    6. Suspected hepatic venous pressure gradient (HVPG) ≥10 mmHg at baseline

    Exclusion Criteria:

    1. Pregnancy or breast feeding

    2. Women of child-bearing potential not using highly effective methods of contraception

    3. Severe liver failure defined by one of the following: Prothrombin activity <40%, Bilirubin >5 mg/dL (85umol/L), hepatic encephalopathy > grade I

    4. A history of variceal bleed within 1 month prior to visit 1

    5. Presence of any non-controlled and clinically significant disease that could affect the study outcome or that would place the patient at undue risk

    6. Hepatocellular carcinoma or history of malignancy of any organ system (other than localized basal cell carcinoma of the skin) treated or untreated

    7. Portal vein thrombosis

    8. Previous surgical shunt or TIPSS

    9. Current use of beta-blockers or nitrates, any other drug therapy known to have an influence on portal pressure (diuretics permitted provided patients have been on a stable dose for at least 30 days)

    10. History of drug or alcohol abuse within 1 month of enrolment

    11. Sitting Systolic Blood Pressure <110 mmHg at screening visit or within 10 minutes prior to starting study drug infusion

    12. Use of other investigational drugs within 5 half-lives of enrolment, or within 30 days/until the expected pharmacodynamic effect has returned to baseline, whichever is longer

    13. Significant arrhythmias, which include any of the following: sustained ventricular tachycardia, bradycardia with sustained ventricular rate < 45 beats per minute or atrial fibrillation/flutter with sustained ventricular response of > 90 beats per minute at rest, or Long QT syndrome or corrected QT interval (QTc) > 450 msec (QT correction will be performed using the Fridericia correction method: QTcF = QT/RR0.33) for males and > 460 msec for females at screening visit

    14. Documented hypersensitivity to intravenous contrast agents and/or iodine

    15. Severe renal impairment (eGFR<30mL/min /1.73m2)

    16. Significant left ventricular outflow tract obstructions (e.g., severe valvular aortic stenosis, obstructive cardiomyopathy), severe mitral stenosis, restrictive amyloid myocardiopathy, acute myocarditis

    17. Severe aortic insufficiency or severe mitral regurgitation for which surgical or percutaneous intervention is indicated

    18. Major neurologic event including cerebrovascular events, within 30 days prior to screening

    19. Clinical evidence of acute coronary syndrome currently or within 30 days prior to enrolment

    20. History of hypersensitivity to study drug serelaxin or study drug ingredients

    21. Inability to follow instructions or comply with follow-up procedures.

    22. Permanent pacemaker, cardiac resynchronisation device or implantable cardioverter-defibrillator in situ

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Liver Unit, Royal Infirmary of Edinburgh Edinburgh United Kingdom EH164TJ

    Sponsors and Collaborators

    • University of Edinburgh
    • Novartis Pharmaceuticals
    • NHS Lothian

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    University of Edinburgh
    ClinicalTrials.gov Identifier:
    NCT02669875
    Other Study ID Numbers:
    • STOPP
    First Posted:
    Feb 1, 2016
    Last Update Posted:
    Oct 11, 2018
    Last Verified:
    Oct 1, 2018
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Liver Cirrhosis
    Hypertension, Portal
    Hypertension
    Fibrosis

    Study Results

    No Results Posted as of Oct 11, 2018